Susceptibility to cocaine addiction may be related to the differential control of a neuronal receptor

Neurons communicate with each other through chemical compounds called neurotransmitters that bind to neuronal receptors in order to transmit information. One of these receptors is the type 1 cannabinoid receptor (CB1), which is involved in numerous neurobehavioural processes and is therefore explored as a target for the treatment of several mental and neurological diseases.

Previous studies show the crucial role that the CB1 receptor plays in addiction, but it is the first time that the differences in the effects that cocaine produces on associative learning processes and sensitivity to cocaine depending on its location in glutamatergic or GABAergic neurons, respectively, have been studied. The results of this research that involves the NeuroPhar research group at the Department of Experimental and Health Sciences (DCEXS) are published in Neurpsychopharmacology.

Glutamatergic neurons produce the glutamate excitatory neurotransmitter while GABAergic neurons synthesise the GABA inhibitory neurotransmitter. By using genetic engineering, scientists inhibited the CB1 receptor in glutamatergic or GABAergic neurons of mice and observed their phenotype during cocaine self-administration. After several behavioural experiments, the experts concluded that the CB1 receptor has a differential control over cocaine consumption according to whether it is located in glutamatergic or GABAergic neurons. For example, mice that lack the CB1 receptor in their GABAergic neurons need a lower dose of cocaine than control mice to obtain the same pleasurable feeling: they were more sensitive to this effect. Thus, CB1 receptors located on GABAergic neurons control sensitivity to the effects of cocaine, while CB1 receptors located on glutamatergic neurons control aspects of cocaine seeking by regulating associative learning processes. These results lead to the conclusion that the susceptibility to cocaine addiction may be influenced by the differential control of CB1 receptors in glutamatergic and GABAergic neurons.

Reference work: Elena Martín-García, Lucie Bourgoin, Adeline Cathala, Fernando Kasanetz, Miguel Mondesir, Ana Gutiérrez-Rodriguez, Leire Reguero, Jean- François Fiancette, Pedro Grandes, Umberto Spampinato, Rafael Maldonado, Pier Vincenzo Piazza, Giovanni Marsicano and Véronique Deroche-Gamonet. Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors. DOI: 10.1038/npp.2015.351. Neuropsychopharmacology, December 2015.